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Combined effect of bisphosphonate and recombinant human bone morphogenetic protein 2 on bone healing of rat calvarial defects

  • Kim, Ho-Chul (Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University) ;
  • Song, Jae-Min (Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University) ;
  • Kim, Chang-Joo (Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University) ;
  • Yoon, Sang-Yong (Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University) ;
  • Kim, In-Ryoung (Department of Oral Anatomy and Cell Biology, School of Dentistry, Pusan National University) ;
  • Park, Bong-Soo (Department of Oral Anatomy and Cell Biology, School of Dentistry, Pusan National University) ;
  • Shin, Sang-Hun (Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University)
  • Received : 2015.04.02
  • Accepted : 2015.05.06
  • Published : 2015.12.31

Abstract

Background: This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects. Methods: Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with $Bio-Oss^{(R)}$ only (group 1, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 (group 2, n = 9), $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and $Bio-Oss^{(R)}$ wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis. Results: There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) decreased with time dependent except group 4. Conclusion: Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast.

Keywords

References

  1. Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone biology and clinical applications. J Bone and Joint Surgery 84:1032-1044 https://doi.org/10.2106/00004623-200206000-00022
  2. Urist MR, Strates BS (1971) Bone morphogenetic protein. J Dent Res 50:1392-1406 https://doi.org/10.1177/00220345710500060601
  3. Gitelman SE, Kobrin MS, Ye JQ, Lopez AR, Lee A, Derynck R (1994) Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo. J Cell Biol 126:1595-1609 https://doi.org/10.1083/jcb.126.6.1595
  4. Wozney JM, Rosen V (1998) Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop 346:26-37
  5. Takaoka K, Yoshikawa H, Hashimoto J, Ono K, Matsui M, Nakazato H (1994) Transfilter bone induction by Chinese hamster ovary (CHO) cells transfected by DNA encoding bone morphogenetic protein-4. Clin Orthop 300:269-273
  6. Cho YJ, Park JW, Bae YC (2008) The effects of synthetic peptide derived from hBMP-2 on bone formation in rabbit calvarial defect. Tissue Eng Regen Me 5:488-497
  7. Cook SD, Wolfe MW, Salkeld SL, Rueger DC (1995) Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates. J Bone and Joint Surgery 77:734-750 https://doi.org/10.2106/00004623-199505000-00010
  8. Green JR (2004) Bisphosphonates: preclinical review. Oncologist 9:3-13
  9. Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Soballe K (2009) Local bisphosphonate treatment increases fixation of hydroxyapatite-coated implants inserted with bone compaction. J Orthop Res 27:189-194 https://doi.org/10.1002/jor.20745
  10. Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115-1117 https://doi.org/10.1016/S0278-2391(03)00720-1
  11. Allen MR, Burr DB (2009) The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67:61-70
  12. Jakobsen T, Kold S, Bechtold JE, Elmengaard B, Soballe K (2006) Effect of topical alendronate treatment on fixation of implants inserted with bone compaction. Clin Orthop Relat Res 444:229-234
  13. Jakobsen T, Kold S, Bechtold J, Elmengaard B, Soballe K (2007) Local alendronate increases fixation of implants inserted with bone compaction: 12-week canine study. J Orthop Res 25:432-441 https://doi.org/10.1002/jor.20276
  14. McLeod K, Anderson GI, Dutta NK, Smart RSC, Voelcker NH, Sekel R et al (2006) Adsorption of bisphosphonate onto hydroxyapatite using a novel co-precipitation technique for bone growth enhancement. J Biomed Mater Res A 79:271-281
  15. McClellan JW, Mulconrey DS, Forbes RJ, Fullmer N (2006) Vertebral bone resorption after transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J Spinal Disord Tech 19:483-486 https://doi.org/10.1097/01.bsd.0000211231.83716.4b
  16. Kim HK, Kim JH, Abbas AA, Yoon TR (2009) Alendronate enhances osteogenic differentiation of bone marrow stromal cells: a preliminary study. Clin Orthop Relat Res 467:3121-3128 https://doi.org/10.1007/s11999-008-0409-y
  17. Lacey D, Timms E, Tan H, Kelley M, Dunstan C, Burgess T et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165-176 https://doi.org/10.1016/S0092-8674(00)81569-X
  18. Tay JY, Bay BH, Yeo JF, Harris M, Meghji S, Dheen ST (2004) Identification of RANKL in osteolytic lesions of the facial skeleton. J Dent Res 83:349-353 https://doi.org/10.1177/154405910408300415
  19. Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ (1993) Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 91:2004-2011 https://doi.org/10.1172/JCI116422
  20. Nishikawa M, Akatsu T, Katayama Y, Yasutomo Y, Kado S, Kugal N et al (1996) Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures. Bone 18:9-14 https://doi.org/10.1016/8756-3282(95)00426-2
  21. Vitte C, Fleisch H, Guenther HL (1996) Bisphosphonates induce osteoblasts to secrete an inhibitor of osteoclast-mediated resorption. Endocrinology 137:2324-2333 https://doi.org/10.1210/endo.137.6.8641182
  22. Naidu A, Dechow PC, Spears R, Wright JM, Kessler HP, Opperman LA (2008) The effects of bisphosphonates on osteoblasts in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106:5-13 https://doi.org/10.1016/j.tripleo.2008.03.036
  23. Srisubut S, Teerakapong A, Vattraphodes T, Taweechaisupapong S (2007) Effect of local delivery of alendronate on bone formation in bioactive glass grafting in rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:e11-e16
  24. Greiner SH, Wildemann B, Back DA, Alidoust M, Schwabe P, Haas NP et al (2008) Local application of zoledronic acid incorporated in a poly (D, L-lactide)-coated implant accelerates fracture healing in rats. Acta Orthop 9:717-725
  25. Roshan-Ghias A, Arnoldi J, Procter P, Pioletti DP (2011) In vivo assessment of local effects after application of bone screws delivering bisphosphonates into a compromised cancellous bone site. Clin Biomech (Bristol, Avon) 26:1039-1043 https://doi.org/10.1016/j.clinbiomech.2011.06.004
  26. Toker H, Ozdemir H, Ozer H, Eren K (2012) Alendronate enhances osseous healing in a rat calvarial defect model. Arch Oral Biol 57:1545-1550 https://doi.org/10.1016/j.archoralbio.2012.06.013
  27. Ficarra G, Beninati F (2007) Bisphosphonate-related osteonecrosis of the jaws: the point of view of the oral pathologist. Clin Cases Miner Bone Metab 4:53-57
  28. Hofbauer LC, Heufelder AE (2001) Role of receptor activator of nuclear factor-${\kappa}B$ ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243-253 https://doi.org/10.1007/s001090100226
  29. Hofbauer LC, Heufelder AE (1998) Osteoprotegerin and its cognate ligand: a new paradigm of osteoclastogenesis. Eur J Endocrinol 139:152-154 https://doi.org/10.1530/eje.0.1390152
  30. Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K, Ueno Y et al (2000) Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function 1. Endocrinology 141:3478-3484 https://doi.org/10.1210/endo.141.9.7634
  31. Levin L, Bryson E, Caplan D, Trope M (2001) Effect of topical alendronate on root resorption of dried replanted dog teeth. Dent Traumatol 17:120-126 https://doi.org/10.1034/j.1600-9657.2001.017003120.x
  32. Shibata T, Komatsu K, Shimada A, Shimoda S, Oida S, Kawasaki K et al (2004) Effects of alendronate on restoration of biomechanical properties of periodontium in replanted rat molars. J Periodont Res 39:405-414 https://doi.org/10.1111/j.1600-0765.2004.00755.x
  33. Komatsu K, Shimada A, Shibata T, Shimoda S, Oida S, Kawasaki K et al (2008) Long-term effects of local pretreatment with alendronate on healing of replanted rat teeth. J Periodont Res 43:194-200 https://doi.org/10.1111/j.1600-0765.2007.01012.x

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